Enigma: Pitt Public Health Researcher Worked to Pinpoint Culprit of Mysterious Illness in Brazil

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At a clinic in the coastal city of Recife, Brazil, pediatric neurologist Vanessa Van der Linden pores over the day’s case files. She has never seen anything like this before. Babies born with microcephaly — abnormally tiny heads and disordered brains — are suddenly appearing in her maternity ward. All of the area’s hospitals combined usually see no more than 10 cases a year. Today alone, she has diagnosed three.

Worry swells in the doctor’s chest. She picks up her cell phone and calls her mother, another pediatric neurologist working in a nearby hospital. “Mommy,” she says in Portuguese. “Há algo errado.” There is something wrong.

Soon, physicians across northeastern Brazil report similar surges of microcephaly cases rising like a tide from the region’s poorest neighborhoods. The search is on to find the cause behind the crisis.

About 10 months before that moment in the clinic, at the start of Brazil’s equatorial rainy season in late 2014, doctors were grappling with a different kind of medical mystery. Reports emerged of an unidentified but seemingly benign illness in the country’s northeast. Its symptoms were graciously mild. Most patients complained of a raised, red skin rash, joint aches and eye irritation. Some had low fevers. The discomfort lasted only a few days and rarely required treatment beyond a pain reliever. No one guessed that it was the first, early sign of new trouble.

Dengue fever, a mosquito-borne viral disease well known to Brazil, also causes fever, rash, and joint pain — but the match wasn’t exact. Dengue, which belongs to the flavivirus genus, is more debilitating. Some infections can generate severe and deadly symptoms, causing hemorrhagic bleeding and joint pain so crushingly intense that a common nickname for the virus is “break-bone fever.”

In the absence of other credible theories and with conflicting lab data, many experts, including those at the Brazilian Ministry of Health, hypothesized that the unknown illness was dengue, but in a mild form. By March 2015, more than 7,000 cases had been reported.

“I have, let’s say, a job-related double personality,” Marques notes with a laugh. His attention often shifts between two different worlds simultaneously — the United States and Brazil, the classroom and the lab, English and Portuguese. But the mystery around the unidentified, enigmatic disease gave the researcher’s focus yet another target.

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Marques grew up in Recife, the grandson of a pharmacist. His father ran the business. As a boy, dark-eyed and curious, Marques would watch as neighbors came to the drugstore for help with what ailed them.

He was still in high school when he decided to become a doctor, but it wasn’t until he reached medical school at Universidade Federal de Pernambuco in Recife that he chose the research track. The detective work of medical research excited him. He loved to explore a problem from all of its angles, delving into its most complex components to better understand its whole.

“I was curious,” he says. “You’re learning these very broad medical theories, and I wanted to know, how did people figure that out? And how could it be done a little better?”

Marques was drawn to translational research — science that could be turned into solutions to major health problems. The study of human immunology, or the way the body’s immune system responds to different diseases, became the lens through which he could investigate viruses and their potential preventative vaccines — particularly those that plague Brazil. He felt something of a duty to serve people in his home country, just as his father and grandfather did.

“Others may have the resources and opportunity to respond to Brazilians’ issues, but they don’t have the actual experience of the reality that the patients live,” Marques says. “I think I can see with the eyes of people who actually have to deal with the problems.”

One problem that Marques saw troubling Brazil was dengue. He zeroed in on the disease, among others, while earning a PhD in pharmacology from Johns Hopkins University. He became a dengue expert, developing new ways to detect its most severe manifestation and inventing a prognostic tool to help doctors predict the health outcomes of dengue-infected patients. But as he finished his postdoctoral work, he knew that to best study dengue and other mosquito-borne diseases, he had to be close to the people most affected.

So there, in the sprawling, beach-lined city where he grew up, Marques built a collaborative lab with one of South America’s most prestigious medical research institutions, Fundação Oswaldo Cruz (FIOCRUZ) Institute. In 2009, when he accepted a professorship at Pitt, the Recife laboratory became one of three international research sites partnered with the University of Pittsburgh Graduate School of Public Health. Marques serves as a liaison between Pitt and FIOCRUZ, connecting scientists from both institutions.

The nature of the research unfolding in the Recife lab is similar to what’s taking place at Pitt’s Center for Vaccine Research, where Marques is also affiliated. It’s translational and incremental, with each study moving researchers closer to unpacking the mysteries of infectious diseases in an effort to better identify, treat and stop them from spreading.

But viruses are particularly tricky subjects. Experience has taught Marques that they are capable of unexpected behavior, and that studying them can be like trying to stare steadily at a moving target. The reach of a virus and its effect on a human host hangs on a multitude of factors including the history of community exposure to similar viruses. Big and small changes in things like environment, human behavior, immune responses or the virus’s genetic composition can alter its scope, allowing it to jump countries or continents, spreading widely or receding quietly. Researchers often aren’t even aware of a virus’s full capability until it is demonstrated by an outbreak. But buried within the structure and behavior of a virus, there are clues about how best to attack it.

At the time of the appearance of the mystery illness, Marques and his lab were focused on a collection of studies investigating dengue immunology. He eyed the “dengue light” outbreak closely, though he remained relatively unconcerned. Whatever it was, it didn’t appear to be dangerous. “That,” he says, “was the assumption.”

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